Description…

Attributes

Datasets

Organs

The following organs have data associated with this biomarker…

Ovary

Attributes

Phase:

Three

QA State:

Accepted

Overview

Overexpression (protein) studies in ovarian cancer.

Performance Comment

Of the 28 ovarian cancer biomarkers tested in prediagnostic specimens, from the PLCO, CA125 remains the the single best biomarker for ovarian cancer and has its strongest signal within six months of diagnosis. CA72-4 alone was not a strong predictor.

Supporting Study Data

The following studies/protocols provide evidence supporting
CA72-4
indications for the
Ovary…

PLCO Ovarian Phase III Validation Study

The obvious appeal of a strategy for the early detection of ovarian cancer is based upon the tendency for the disease to present at advanced stages associated with poor survival. If the diagnosis could be largely shifted to stages I or II associated with survival close to 90%, then the overall mortality for this disease could be dramatically altered without any advances in therapy. While approaches to ovarian cancer screening might include pelvic examination or sonography, a vast amount of information exists on potential blood markers for the disease. The precision of sensitivity and specificity estimates will be greater for larger versus smaller study populations; but the effect produced by differences in the populations studied cannot as easily be predicted. Most of the studies relied on phase II validation (i.e. case vs. control differences); but case groups may differ by disease stage and histology that may affect overall estimates of sensitivity. Many studies have limited case specimens to those collected pre-operatively, but not all were explicit in this regard. Few studies have used pre-diagnostic sera months or years before diagnosis, so-called Phase III studies. Similarly, the nature of the control group will also affect specificity estimates. Inclusion of surgical controls that have benign gynecological conditions such as fibroids, endometriosis, or benign ovarian tumors may elevate marker levels and lower specificity. One strategy, besides combining markers, to improve the sensitivity and/or specificity would be to use marker history in the context of serial testing. Elevated but declining marker levels would indicate a transient condition associated with marker production. Elevated but stable levels might indicate chronic but benign conditions associated with marker production, while elevated and increasing levels are more likely indicative of cancer. Our hypothesis is that a panel of biomarkers will have better performance characteristics as a screening test for pre-clinical ovarian cancer than any single marker, and yield a longer lead time than CA125 alone.

Biomarker Characteristics Summary

Notes

Sensitivity

Specificity

Prevalence

NPV

PPV

Specific Assay Type

Cases with diagnosis of ovarian cancer (on average) 9 months prior to collection. Controls were matched to cases by age and timing of specimen collection including general population controls (50%), false positive CA125 (25%), and family history of breast cancer (25%). All cases (n=60).

Study-Specific Resources

No study-specific resources defined.

SPORE/EDRN/PRE-PLCO Ovarian Phase II Validation Study

Phase II specimens from 160 ovarian cancer cases and 640 benign disease or general population controls were assembled from four Early Detection Research Network (EDRN) or Ovarian Cancer Specialized Program of Research Excellence (SPORE) sites and used to rank 51 biomarkers. Top markers in phase II specimens included CA125, HE4, transthyretin, CA15.3, and CA72.4 with sensitivity at 95% specificity ranging from 0.73 to 0.40.

Biomarker Characteristics Summary

For all cases, using all controls. Results from preliminary analysis, 50% of 114 sample set. Daniel Cramer laboratory.

25.0

95.0

N/A

N/A

N/A

For early stage (more than 12 months prior to diagnosis), using all controls. Results from preliminary analysis, 50% of 114 sample set. Daniel Cramer laboratory.

34.0

95.0

N/A

N/A

N/A

For late stage (within 12 months of diagnosis), using all controls. Results from preliminary analysis, 50% of 114 sample set. Daniel Cramer laboratory.

9.0

95.0

N/A

N/A

N/A

Cases with diagnosis of ovarian cancer (on average) 9 months prior to collection. Controls were matched to cases by age and timing of specimen collection including general population controls (50%), false positive CA125 (25%), and family history of breast cancer (25%). All cases (n=60).

Resources

The next EDRN Steering Committee Meeting will take place March 31st through April 2nd, 2015, in Atlanta, Georgia.

Announcement 02/12/2015

Please register for the 29th EDRN Steering Committee Meeting in Atlanta, GA from March 31-April 2, 2015. The registration page has information about booking hotel rooms and a draft agenda of the meeting.